Nucleophilic addition of benzenethiol to 1′,2′-unsaturated nucleosides: 1′-C-phenylthio-2′-deoxynucleosides as anomeric radical precursors

Article abstract of DOI:10.1021/jo0201934

The addition reaction of benzenethiol to the glycal portion of 1′,2′-unsaturated uridine proceeds efficiently in the presence of Et₃N. The mechanism involves nucleophilic attack of thiolate at the anomeric position in the rate-determining step, wherein conjugation between the nucleobase and the glycal portion is crucial. The derivative having a methyl group either at the 2′- or 6-position did not undergo this addition reaction, due to their sterically prohibited coplanarity. The 1′,2′-unsaturated derivatives of thymine and adenine can also be used as substrates for this addition reaction. It was also shown that the resulting 1′-C-phenylthio-2′-deoxynucleosides serve as precursors for radical-mediated C-C bond formation at the anomeric position.

Full text of DOI:10.1021/jo0201934

Nu cleop h ilic Ad d ition of Ben zen eth iol to 1′,2′-Un sa tu r a ted
Nu cleosid es: 1′-C-P h en ylth io-2′-d eoxyn u cleosid es a s An om er ic
Ra d ica l P r ecu r sor s
Hiroki Kumamoto, Miki Murasaki, Kazuhiro Haraguchi, Aki Anamura, and
Hiromichi Tanaka*
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku,
Tokyo 142-8555, J apan
hirotnk@pharm.showa-u.ac.jp
Received March 19, 2002
The addition reaction of benzenethiol to the glycal portion of 1′,2′-unsaturated uridine proceeds
efficiently in the presence of Et3N. The mechanism involves nucleophilic attack of thiolate at the
anomeric position in the rate-determining step, wherein conjugation between the nucleobase and
the glycal portion is crucial. The derivative having a methyl group either at the 2′- or 6-position
did not undergo this addition reaction, due to their sterically prohibited coplanarity. The 1′,2′-
unsaturated derivatives of thymine and adenine can also be used as substrates for this addition
reaction. It was also shown that the resulting 1′-C-phenylthio-2′-deoxynucleosides serve as
precursors for radical-mediated C-C bond formation at the anomeric position.
SCHEME 1
In tr od u ction
Although interest regarding the addition reaction of
thiols to C-C double bonds have mostly been devoted to
those operated by a free radical chain mechansm,1 the
reaction also occurs by the usual electrophilic ionic
mechanism. Parham and DeLaitsch reported that, in the
presence of a catalytic amount of anhydrous HCl in Et2O,
benzenethiol reacts with 3,4-dihydro-2H-pyran to yield
phenyl 2-tetrahydropyranyl sulfide, albeit at an ap-
preciably slower rate than does the oxygen counterpart
phenol.2
In our previous studies on the chemistry of the 1′,2′-
unsaturated uridine, 1-(2-deoxy-D-erythro-pent-1-eno-
furanosyl)uracil,3-5 it was shown that the 3′,5′-bis-O-tert-
butyldimethylsilyl (TBDMS) derivative 1 undergoes elec-
trophilic addition (bromo-pivaloyloxylation) to give 2
which can be used as a common intermediate for the
synthesis of 1′-C-branched derivatives 3 by reacting with
organosilicon or organoaluminum reagents (Scheme 1).3
It was also shown that 2 undergoes radical-mediated 1,2-
acyloxy migration to form an anomeric radical 4.4
In the present study, the introduction of a radical
precursor, a phenylthio group, to the anomeric position
of 1 and other 1′,2′-unsaturated nucleosides was inves-
tigated. Also described here is use of the resulting 1′-C-
phenylthio-2′-deoxynucleosides as anomeric radical pre-
cursors, which allows the synthesis of 1′-C-branched 2′-
deoxynucleosides.
(1) Stacey, F. W.; Harris, J . F., J r. In Organic Reactions; 1963; Vol.
13, Chapter 4.
(2) Parham, W. E.; DeLaitsch, D. M. J . Am. Chem. Soc. 1954, 76,
4962-4965.
(3) Itoh, Y.; Haraguchi, K.; Tanaka, H.; Gen, E.; Miyasaka, T. J .
Org. Chem. 1995, 60, 656-662.
(4) Itoh, Y.; Haraguchi, K.; Tanaka, H.; Matsumoto, K.; Nakamura,
K. T.; Miyasaka, T. Tetrahedron Lett. 1995, 36, 3867-3870.
(5) Kumamoto, H.; Shindoh, S.; Tanaka, H.; Itoh, Y.; Haraguchi,
K.; Gen, E.; Kittaka, A.; Miyasaka, T.; Kondo, M.; Nakamura, K. T.
Tetrahedron 2000, 56, 5363-5371.
Ad d it ion of Ben zen et h iol t o 1′,2′-Un sa t u r a t ed
Nu cleosid es. The starting material 1 can be prepared
from 3′,5′-bis-O-TBDMS-O2,2′-anhydrouridine either by
10.1021/jo0201934 CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/26/2002
6124
J . Org. Chem. 2002, 67, 6124-6130

1′-C-Phenylthio-2′-deoxynucleosides
the original method of Robins and Trip6 or by the method
reported from our laboratory: the anhydro-bond cleavage
with (PhSe)2/LiAlH4 followed by oxidative elimination of
PhSeOH.7
SCHEME 2
Compound 1 has the inherent propensity to undergo
aromatization to form the furan derivative 58 and shows
the UV absorption maximum (λmax) in MeOH at a
significantly longer wavelength of 276 nm as compared
with those of usual uridine analogues, for example,
2′,3′,5′-tris-O-TBDMS-uridine (λmax in MeOH: 262 nm).
In our recent study on the synthesis of the 2′-substituted
derivatives of 1,5 it was shown that these characteristic
properties of 1, both chemical and spectroscopic, can be
attributable to its planar disposition between the base
and glycal moieties.
reaction time to 0.5 h (yield of adduct: 88%), while
p-methoxybenzenethiol (pKa 6.775)9) required 5 h (yield
of adduct: 98%) for completion. These results suggest
that the efficient addition of PhSH to 1 takes place
through a nucleophilic ionic mechanism. This features
conjugation between the base and glycal moieties, shown
as the resonance structure 1a in Scheme 2, that is crucial
for the nucleophilic attack of benzenethiolate in the rate-
determining step.
Such conjugation is not feasible in the cases of the 2′-
substituted and 6-substituted derivatives of 1, because
these substituents by occupying ortho position of the N1-
C1′ pivot bond prevent the molecule from taking a
coplanar conformation.5 When the 2′-methyl derivative
7 (λmax in MeOH: 255 nm) or the 6-methyl derivative 8
(λmax in MeOH: 257 nm) was reacted with PhSH in CH3-
CN in the presence of Et3N, only recovery of the starting
material was observed (7, 73%;12 8, 93%). It was also
confirmed that a simple glycal such as 3,4,6-tri-O-
benzylglucal (9) does not react with PhSH under these
conditions.
Our major concern in starting the present study with
the introduction of a phenylthio group as a radical
precursor to the anomeric position of 1 was the antici-
pated formation of the furan derivative 5 which would
be accelerated by the acidic reagent benzenethiol (pKa
6.615).9 In fact, even when 1 was reacted with PhSH (15
equiv) in CH2Cl2 in the absence of any additional acid
catalyst like anhydrous HCl, 5 was formed in 21% yield.
Although this reaction also gave the desired adduct 6 (a
mixture of two diastereomers: 6â/6r ) 27/73)10 in 50%
yield, the progress of the addition reaction was extremely
sluggish and consequently required stirring for 5 days
at room temperature.
To investigate stereochemical aspects (syn- or anti-
addition) of this reaction, the 2′-deuterated derivative (1-
D) was prepared from 1 as shown in Scheme 3. Com-
pound 2 prepared in our previous study3 was reacted with
silylated PhSH in the presence of SnCl4 to give 10
SCHEME 3
In contrast, the presence of Et3N (5 equiv) in the above
reaction mixture greatly enhanced the reaction rate to
give 6 (6â/6r ) 9/91) in 87% yield after only 1 h with no
detectable amount of 5 being formed. The highest yield
of 6 (94%, 6â/6r ) 15/85) was observed when the reaction
was carried out in CH3CN (PhSH, 15 equiv; Et3N, 5
equiv) at room temperature for 1 h.11 It is worth noting
that the reaction time for completion of this addition
reaction depends on the acidity of benzenethiols. Thus,
the use of p-nitrobenzenethiol (pKa 4.715)9 shortened the
(6) Robins, M. J .; Trip, E. M. Tetrahedron Lett. 1974, 3369-3372.
(7) Haraguchi, K.; Tanaka, H.; Maeda, H.; Itoh, Y.; Saito, S.;
Miyasaka, T. J . Org. Chem. 1991, 56, 5401-5408.
(8) For physical data of 5, see ref 7.
(9) Data (measured in water at 25 °C) taken from the following
report: De Maria, P.; Fini, A.; Hall, F. M. J . Chem. Soc., Perkin Trans.
2 1973, 1969-1971.
(10) The depicted stereochemistry of 6â and 6r was determined by
the following NOE data: 6â (1% between H-5′ and H-6; 3% between
H-4′ and ortho-proton of SPh); 6r (1% between H-5′ and ortho-proton
of SPh).
(11) A similar anomer ratio was observed when 3′,5′-O-(di-tert-
butylsilylene) derivative was reacted with PhSH under these reaction
conditions (yield 75%, â/R ) 13/87).
J . Org. Chem, Vol. 67, No. 17, 2002 6125

Kumamoto et al.
stereoselectively in 86% yield. This compound was found
to be rather unstable, and further treatment with DBN
in CH3CN gave the 2′-C-phenylthio-1′,2′-unsaturated
uridine (11) in 80% yield as a result of 1,2-migration of
the phenylthio group. Oxidation of 11 with m-CPBA gave
the sulfoxide 12 (89%). Deuteration at the 2′-position was
carried out based on the reported ligand exchange
reaction of sufoxides13 by reacting 12 with EtMgBr and
then by quenching with CH3OD. Compound 1-D was
obtained in 71% yield with a deuterium incorporation of
57%.
to give 15 (â/R ) 6/94) in 88% yield after 1 h. The 1′,2′-
unsaturated adenosine 16,16 on the other hand, required
heating in refluxing CH3CN for 18 h to form the adduct
17 (76%, â/R ) 24/76).
R a d ica l R ea ct ion s of 1′-C-P h en ylt h io-2′-d eoxy-
r ibon u cleosid es. As shown in Scheme 4, radical-medi-
ated allylation at the anomeric position was carried out
The addition reaction of PhSH to 1-D (Et3N/CH3CN,
for 1 h) was followed by HPLC separation of the resulting
adducts (6â-D/6r-D ) 15/85). Based on the analysis of
1
SCHEME 4
their H NMR spectra, it became apparent that exclusive
syn-addition had taken place for the major isomer 6r,
while both the syn- and anti-pathway (syn/anti ) 1.8/
1.0) had been operative in the formation of 6â. We have
no satisfactory explanation for these results, but as far
as formation of the major adduct 6r is concerned, it would
be possible to say that the R-face of the incipient C2′-
anion is more encumbered than the â-face due to the
presence of both the uracil base and the 3′-O-silyl group.
One would readily anticipate that the phenylselenenyl
group can also serve as an anomeric radical precursor.
The adduct 13 was prepared in 96% yield (â/R ) 17/83)
by reacting 1 with benzeneselenol under the same
reaction conditions as those employed for the formation
of 6. Compound 13 was found, however, to be too labile,
liberating benzeneselenol upon heating in refluxing
benzene to yield 1.14
in benzene by using 6 (6â/6r ) 15/85) and allyl(tributyl)-
tin or allyl(triphenyl)tin under several different reaction
conditions: Et3B/0 °C; (Bu3Sn)2/hν/rt; AIBN/80 °C. Al-
though the yield of the product (18) varied considerably
(51%-82%) depending on the conditions used, there was
no significant difference in the ratio of 18â/18r (67/33-
72/28). The highest yield of 82% was attained with a
diastereomeric ratio of 18â/18r ) 68/32 upon reacting
with allyl(tributyl)tin in the presence of AIBN in reflux-
ing benzene for 2 h. Compounds 18â and 18r were
isolated by HPLC separation (hexane/EtOAc ) 5/1, 18â
tR 41 min; 18r tR 40 min). Predominant formation of
â-anomer was also observed in the allylation of 15 and
17, forming 19â (combined yield 81%, â/R ) 68/32) and
20â (combined yield 72%, â/R ) 71/29), respectively, as
the major product.17
The present addition reaction also works for other 1′,2′-
unsaturated nucleosides. The thymine derivative 1415
reacts with PhSH/Et3N in CH3CN at room temperature
(12) This particular reaction was carried out in refluxing CH3CN
for 12 h.
(13) Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Matsuda, K.;
Koyama, M. Tetrahedron 1998, 54, 5557-5574.
(14) Introduction of a phenylselenenyl group to the anomeric position
of a 2′- ketouridine has recently been reported: Kodama, T.; Shuto,
S.; Nomura, M.; Matsuda, A. Chem. Eur. J . 2001, 7, 2332-2340.
(15) For the preparation of 14 from 3′,5′-bis-O-(tert-butyldimethyl-
silyl)- O2,2′-anhydroribothymidine: Yoshimura, Y.; Kano, F.; Miyazaki,
S.; Ashida, N.; Sakata, S.; Haraguchi, K.; Itoh, Y.; Tanaka, H.;
Miyasaka, T. Nucleosides Nucleotides 1996, 15, 305.
Chatgilialoglu et al. reported that the 2′-deoxyuridin-
1-yl radical derived from 1′-C-(tert-butyl)carbonyl-2′-
(16) For the preparation of 16: Gimisis, T.; Ialongo, G.; Chatgilia-
loglu, C. Tetrahedron 1998, 54, 573-592.
(17) Stereochemistry of the â- and R-anomers of 18, 19, and 20 was
determined by the following NOE data: 18â (1% between H-3′ and
H- 6); 18r (9% between H-4′ and H-6); 19â (1% between H-3′ and
H-6); 19r (10% between H-4′ and H-6); 20â (1% between H-3′ and H-8);
20r (9% between H-4′ and H-8).
6126 J . Org. Chem., Vol. 67, No. 17, 2002

1′-C-Phenylthio-2′-deoxynucleosides
26). In the reaction with methyl acrylate, to ensure a
high-yield of 23 (72%, â/R ) 70/30), it was necessary to
add a benzene solution of AIBN dropwise to a refluxing
mixture containing 6, the acceptor, and Bu3SnH.22
Con clu sion
Characteristic coplanar disposition of nucleobase and
glycal portions of 1′,2′-unsaturated nucleosides has al-
lowed an efficient nucleophilic addition reaction with
PhSH accelerated by Et3N. Through this addition reac-
tion, 1′-C-phenylthio derivatives of 2′-deoxyuridine, thy-
midine, and 2′-deoxyadenosine were prepared as an
anomeric mixture with the respective R-anomer being
preponderant. The phenylthio group of these adducts
serves as a radical precursor upon reacting with allyl-
(tributyl)tin, acrylonitrile/Bu3SnH, and methyl acrylate/
Bu3SnH in refluxing benzene in the presence of AIBN.
The whole reaction sequence constitutes an efficient entry
to 1′-C-branched 2′-deoxynucleosides.
deoxyuridine18 as being pyramidal based on EPR spec-
troscopy.19 Also reported was the observation that both
â- and R- anomers of this radical precursor gave an
identical â/R-ratio (65/35) of 2′-deoxyuridine upon ir-
radiation in the presence of various thiols as hydrogen
donors.20 These facts have led to the proposal that the
2′-deoxyuridin-1-yl radical exists in equilibrium of two
sp3-hybridized species with opposite configuration. This
was further supported in the present reaction of 6. Thus,
when 6â and 6r were reacted separately with allyl-
(tributyl)tin, exactly the same ratio of 18â/18r ) 68/32
resulted.
Finally, radical reactions of 6 with acceptors such as
acrylonitrile and methyl acrylate were carried out by
using Bu3SnH (1.0 equiv)/AIBN (0.4 equiv) in refluxing
benzene. In these reactions, incipient radical formed by
addition of the anomeric radical to the acceptor has a
good chance to cyclize across the 5,6-double bond in a
5-exo-trig manner.21 In fact, when a refluxing mixture of
6 and acrylonitrile (5 equiv) was treated with Bu3SnH/
AIBN added dropwise over 4 h via a motor-driven syringe
and then the reaction continued for further 3 h, in
addition to the desired product 21 (24%), the 6,1′-ethano-
bridged product 22 (41%, a diastereomeric mixture) was
Exp er im en ta l Section
1
Melting points are uncorrected. H NMR was measured at
500 MHz. Chemical shifts are reported relative to Me4Si. Mass
spectra (MS) were taken in FAB mode with m-nitrobenzyl
alcohol as a matrix. Column chromatography was carried out
on silica gel (Silica Gel 60) unless otherwise noted. Thin-layer
chromatography (TLC) was performed on silica gel (precoated
silica gel plate F254). HPLC was carried out on a 2 × 25 cm
column.
3′,5′-Bis-O-(ter t-bu tyld im eth ylsilyl)-2′-d eoxy-1′-C-p h en -
ylth iou r id in e (6â) a n d Its An om er (6r). A mixture of 1 (100
mg, 0.22 mmol), PhSH (0.34 mL, 3.3 mmol), and Et3N (0.15
mL, 1.1 mmol) in CH3CN (3.0 mL) were stirred at room
temperature for 1 h under positive pressure of dry Ar. The
reaction mixture was partitioned between CHCl3 and satu-
rated aqueous NaHCO3. Column chromatography (hexane/
EtOAc ) 3/1) of the organic layer gave 6 (117 mg, 94%, powder)
as a mixture of 6â/6r ) 27/73 (calculated by integrating H-5).
HPLC (hexane/EtOAc ) 2/1) separation of this mixture gave
analytically pure 6â (tR 18 min, foam) and 6r (tR 14 min, solid).
Physical data of 6â: UV (MeOH) λmax 265 nm (ꢀ 9400), λmin
241 nm (ꢀ 2400); 1H NMR (CDCl3) δ 0.03, 0.08, and 0.10 (12H,
each as s), 0.84 and 0.92 (18H, each as s), 2.77 (1H, dd, J )
4.0 and 15.0 Hz), 3.03 (1H, dd, J ) 7.2 and 15.0 Hz), 3.71 (1H,
dd, J ) 3.5 and 11.5 Hz), 3.80 (1H, dd, J ) 2.9 and 11.5 Hz),
4.28-4.33 (2H, m), 5.16 (1H, dd, J ) 2.5 and 8.1 Hz), 7.09
(1H, d, J ) 8.1 Hz), 7.25-7.29, 7.35-7.38, and 7.41-7.43 (5H,
each as m), 8.36 (1H, br); FAB-MS m/z 603 (M+ + K). Anal.
Calcd for C27H44N2O5SSi2: C, 57.41; H, 7.85; N, 4.96. Found:
C, 57.71; H, 8.11; N, 4.89. Physical data of 6r: mp 161 °C;
1
UV (MeOH) λmax 266 nm (ꢀ 10400), λmin 239 nm (ꢀ 1900); H
NMR (CDCl3) δ -0.01 and 0.10 (12H, each as s), 0.76 and 0.92
(18H, each as s), 2.58 (1H, dd, J ) 5.5 and 14.5 Hz), 3.37 (1H,
dd, J ) 2.5 and 14.5 Hz), 3.41 (1H, dd, J ) 6.4 and 11.0 Hz),
3.66 (1H, dd, J ) 4.6 and 11.0 Hz), 4.01 (1H, ddd, J ) 2.3, 4.6,
and 6.4 Hz), 4.30 (1H, ddd, J ) 2.3, 2.5, and 5.5 Hz), 5.34 (1H,
dd, J ) 2.5 and 8.3 Hz), 7.26-7.51 (6H, m), 8.27 (1H, br); FAB-
MS m/z 603 (M+ + K). Anal. Calcd for C27H44N2O5SSi2: C,
57.41; H, 7.85; N, 4.96. Found: C, 57.45; H, 8.00; N, 4.88.
1-[2-Br om o-3,5-bis-O-(ter t-bu tyld im eth ylsilyl)-2-d eoxy-
1-p h en ylth io-â-D-a r a bin ofu r a n osyl]u r a cil (10). A mixture
of benzenethiol (0.13 mL, 1.26 mmol) and N,O-bis(trimethyl-
silyl)acetamide (0.31 mL, 1.26 mmol) in CH2Cl2 (3 mL) was
also formed. Simply by adding Bu3SnH/AIBN over a
considerably shorter time of 1 h, formation of 22 was
suppressed, and 21 was isolated in 83% yield (â/R ) 74/
(18) (a) Goodman, B. K.; Greenberg, M. M. J . Org. Chem. 1996, 61,
2-3. (b) Greenberg, M. M.; Yoo, D. J .; Goodman, B. K. Nucleosides
Nucleotides 1997, 16, 33-40.
(19) Chatgilialoglu, C.; Gimisis, T.; Guerra, M.; Ferreri, C.; Emanuel,
C. J .; Horner, J . H.; Newcomb, M.; Lucarini, M.; Pedulli, G. F.
Tetrahedron Lett. 1998, 39, 3947-3950.
(20) Chatgilialoglu, C.; Ferreri, C.; Bazzanini, R.; Guerra, M.; Choi,
S.-Y.; Emanuel, C. J .; Horner, J . H.; Newcomb, M. J . Am. Chem. Soc.
2000, 122, 9525-9533.
(22) Stereochemistry of the â- and R-anomers of 21 and 23 was
determined by the following NOE data: 21â (1% between H-3′ and
H-6, 5% between H-5′ and H-6); 21r (9% between H-4′ and H-6); 23â
(1% between H-3′ and H-6); 23r (10% between H-4′ and H-6).
(21) For a recent example: Kumamoto, H.; Ogamino, J .; Tanaka,
H.; Suzuki, H.; Haraguchi, K.; Miyasaka, T.; Yokomatsu, T.; Shibuya,
S. Tetrahedron 2001, 57, 3331-3341.
J . Org. Chem, Vol. 67, No. 17, 2002 6127

Kumamoto et al.
stirred for 1 h at room temperature under positive pressure
of dry Ar and then cooled to -40 °C. After a solution of 2 (400
mg, 0.63 mmol) in CH2Cl2 (3 mL) was added dropwise to the
above mixture, the reaction was continued for 2 h at -20 °C.
(1H, dd, J ) 2.6 and 8.0 Hz), 7.15 (1H, d, J ) 8.0 Hz), 7.22-
7.28 (2H, m), 7.34-7.38 (1H, m), 7.52-7.55 (2H, m), 7.98 (1H,
br); FAB-MS m/z 501 (M+ - uracil - H). Anal. Calcd for
C
27H44N2O5SeSi2: C, 53.01; H, 7.25; N, 4.58. Found: C, 52.96;
H, 7.58; N, 4.87.
The reaction mixture was partitioned between saturated
aqueous NaHCO3 and CHCl3. Column chromatography (hex-
ane/EtOAc ) 3/1) of the organic layer gave 10 (348.5 mg, 86%)
as a foam, which is rather unstable: 1H NMR (CDCl3) δ 0.08,
0.09, 0.15, and 0.20 (12H, each as s), 0.91 and 0.97 (18H, each
as s), 3.87 (1H, dd, J ) 5.3 and 11.0 Hz), 3.91 (1H, dd, J ) 5.8
and 11.0 Hz), 4.49 (1H, ddd, J ) 3.6, 5.3, and 5.8 Hz), 4.65
(1H, d, J ) 3.6 Hz), 4.89 (1H, s), 5.24 (1H, dd, J ) 2.6 and 8.3
Hz), 7.01 (1H, d, J ) 8.3 Hz), 7.26-7.31 (2H, m), 7.36-7.40
(3H, m), 8.13 (1H, br). Without any further characterization,
this compound was used for the preparation of 11.
1-[3,5-Bis-O-(ter t-bu tyld im eth ylsilyl)-2-d eoxy-2-p h en -
ylth io-D-er yth r o-p en t-1-en ofu r a n osyl]u r a cil (11). DBN
(0.33 mL, 2.65 mmol) was added dropwise to a CH3CN (8 mL)
solution of 10 (341.3 mg, 0.53 mmol) kept at 0 °C under
positive pressure of dry Ar. After stirring overnight at room
temperature, the reaction mixture was partitioned between
brine and EtOAc. Column chromatography (hexane/EtOAc )
3/1) of the organic layer gave 11 (259.6 mg, 87%) as a pale
yellow foam: UV (MeOH) λmax 249 nm (ꢀ 17400), λmin 230 nm
(ꢀ 10800); 1H NMR (CDCl3) δ -0.03, 0.08, and 0.09 (12H, each
as s), 0.85 and 0.90 (18H, each as s), 3.80 (1H, dd, J ) 6.0 and
11.0 Hz), 3.88 (1H, dd, J ) 4.4 and 11.0 Hz), 4.53-4.56 (1H,
m), 4.93 (1H, d, J ) 2.8 Hz), 5.71 (1H, dd, J ) 2.2 and 8.2 Hz),
7.12-7.18 (2H, m), 7.23-7.30 (4H, m), 8.32 (1H, br); FAB-MS
m/z 563 (M+ + H). Anal. Calcd for C27H42N2O5SSi2: C, 57.61;
H, 7.52; N, 4.98. Found: C, 57.57; H, 7.61; N, 4.91.
1-[3,5-Bis-O-(ter t-bu tyld im eth ylsilyl)-2-d eoxy-2-p h en -
ylsu lfin yl-D-er yth r o-pen t-1-en ofu r an osyl]u r acil (12). Com-
pound 11 (188 mg, 0.33 mmol) dissolved in CH2Cl2 (6 mL) was
kept at -50 °C. A CH2Cl2 (3 mL) solution of m-CPBA (min
65%, 133.1 mg, 0.5 mmol) was added dropwise to the above
solution, and the reaction mixture was stirred for 2 h at -50
°C. The reaction mixture was partitioned between saturated
aqueous NaHCO3 and CHCl3. Column chromatography (hex-
ane/EtOAc ) 1/1) of the organic layer gave 12 (172.7 mg, 90%,
ratio of diastereomers ) 88/22) as a foam: UV (MeOH) λmax
257 nm (ꢀ 13600), λmin 245 nm (ꢀ 13300); 1H NMR (CDCl3) data
of the major diastereomer δ -0.32, -0.02, and 0.09 (12H, each
as s), 0.73 and 0.91 (18H, each as s), 3.73 (1H, dd, J ) 5.6 and
11.2 Hz), 3.80 (1H, dd, J ) 4.9 and 11.2 Hz), 4.53 (1H, ddd, J
) 2.0, 4.9, and 5.6 Hz), 5.21 (1H, d, J ) 2.0 Hz), 5.83 (1H, d,
J ) 8.0 Hz), 7.38-7.54 (4H, m), 7.80-7.83 (2H, m), 8.27 (1H,
br); FAB-MS m/z 579 (M+ + H). Anal. Calcd for C27H42N2O6-
SSi2: C, 56.02; H, 7.31; N, 4.84. Found: C, 56.15; H, 7.46; N,
4.74.
P r ep a r a tion of th e 2′-Deu ter a ted 1′,2′-Un sa tu r a ted
Ur id in e (1-D). A THF solution of EtMgBr (0.96 M, 3.92 mL,
3.76 mmol) was added dropwise to 12 (436.1 mg, 0.75 mmol)
in THF (18 mL) kept at -40 °C under positive pressure of dry
Ar. After stirring for 1 h, the reaction mixture was treated
with MeOD (5 mL) and then partitioned between brine and
CHCl3. Florisil column chromatography (hexane/EtOAc ) 5/1)
of the organic layer gave 1-D (241.5 mg, 71%) as a powder.
The extent of deuterium incorporation (57%) was calculated
based on 1H NMR spectroscopy by integrating H-2′.
Physical data of 13r: mp 157-159 °C; UV (MeOH) λmax 268
1
nm (ꢀ 10900), λmin 246 nm (ꢀ 6800); H NMR (CDCl3) δ -0.02
and 0.06 (12H, each as s), 0.75 and 0.90 (18H, each as s), 2.64
(1H, dd, J ) 5.1 and 14.8 Hz), 3.17 (1H, dd, J ) 6.8 and 11.0
Hz), 3.40 (1H, dd, J ) 2.2 and 14.8 Hz), 3.50 (1H, dd, J ) 4.6
and 11.0 Hz), 4.02 (1H, ddd, J ) 2.1, 4.6, and 6.8 Hz), 4.23
(1H, ddd, J ) 2.1, 2.2, and 5.1 Hz), 5.42 (1H, dd, J ) 2.5 and
8.5 Hz), 7.26-7.30 (2H, m), 7.37-7.44 (2H, m), 7.60-7.62 (2H,
m), 8.16 (1H, br); FAB-MS m/z 501 (M+ - uracil - H). Anal.
Calcd for C27H44N2O5SeSi2: C, 53.01; H, 7.25; N, 4.58. Found:
C, 53.14; H, 7.42; N, 4.82.
3′,5′-Bis-O-(ter t-b u t yld im et h ylsilyl)-1′-C-p h en ylt h io-
th ym id in e (15â) a n d Its r-An om er (15r). A mixture of these
two anomers (â/R ) 24/76, calculated by integrating H-2′) was
obtained in 88% yield from 14 by the procedure described for
the preparation of 6. HPLC (hexane/EtOAc ) 2/1) separation
of this mixture gave analytically pure 15â (tR 9.0 min, foam)
and 15r (tR 7.4 min, foam). Physical data of 15â: UV (MeOH)
λ
max 268 nm (ꢀ 16100), λmin 247 nm (ꢀ 11800); 1H NMR (CDCl3)
δ 0.04, 0.08, and 0.10 (12H, each as s), 0.84 and 0.92 (18H,
each as s), 1.54 (3H, d, J ) 1.3 Hz), 2.75 (1H, dd, J ) 3.9 and
15.0 Hz), 3.03 (1H, dd, J ) 7.6 and 15.0 Hz), 3.73 (1H, dd, J
) 4.0 and 11.6 Hz), 3.83 (1H, dd, J ) 2.8 and 11.6 Hz), 4.26-
4.29 (1H, m), 4.32-4.35 (1H, m), 6.90 (1H, q, J ) 1.3 Hz), 7.25-
7.29 (2H, m), 7.32-7.36 (1H, m), 7.42-7.44 (2H, m), 8.20 (1H,
br); FAB-MS m/z 617 (M+ + K). Anal. Calcd for C28H46N2O5-
SSi2: C, 58.09; H, 8.01; N, 4.84. Found: C, 58.29; H, 8.28; N,
4.69. Physical data of 15r: UV (MeOH) λmax 268 nm (ꢀ 13800),
λmin 245 nm (ꢀ 9500); 1H NMR (CDCl3) δ -0.02 and 0.09 (12H,
each as s), 0.74 and 0.92 (18H, each as s), 1.70 (3H, d, J ) 1.2
Hz), 2.58 (1H, dd, J ) 5.7 and 14.7 Hz), 3.34 (1H, dd, J ) 3.1
and 14.7 Hz), 3.35 (1H, dd, J ) 6.5 and 11.0 Hz), 3.63 (1H,
dd, J ) 4.6 and 11.0 Hz), 4.00 (1H, ddd, J ) 2.8, 4.6, and 6.5
Hz), 4.22 (1H, ddd, J ) 2.8, 3.1, and 5.7 Hz), 7.20 (1H, q, J )
1.2 Hz), 7.28-7.32 (2H, m), 7.35-7.39 (1H, m), 7.51-7.53 (2H,
m), 8.16 (1H, br); FAB-MS m/z 617 (M+ + K). Anal. Calcd for
C
28H46N2O5SSi2: C, 58.09; H, 8.01; N, 4.84. Found: C, 58.25;
H, 8.15; N, 4.86.
3′,5′-Bis-O-(ter t-bu tyld im eth ylsilyl)-2′-d eoxy-1′-C-p h en -
ylth ioa d en osin e (17â) a n d Its r-An om er (17r). A mixture
of 16 (300 mg, 0.63 mmol), PhSH (0.97 mL, 9.45 mmol), and
Et3N (0.44 mL, 3.15 mmol) in CH3CN (15 mL) was refluxed
for 24 h under atmosphere of dry Ar.
The reaction mixture was partitioned between CHCl3 and
saturated aqueous NaHCO3. Column chromatography (hexane/
EtOAc ) 1/2) of the organic layer gave 17 (280.3 mg, 76%) as
a mixture of 17â/17r ) 24/76 (calculated by integrating H-2′).
HPLC (hexane/EtOAc ) 1/1) separation of this mixture gave
analytically pure 17â (tR 29.4 min, solid) and 17r (tR 25.9 min,
solid). Physical data of 17â: mp 145-148 °C; UV (MeOH) λmax
260 nm (ꢀ 16100), λmin 238 nm (ꢀ 7100); 1H NMR (CDCl3) δ
0.02, 0.05, and 0.08 (12H, each as s), 0.81 and 0.90 (18H, each
as s), 2.80 (1H, dd, J ) 6.1 and 14.3 Hz), 3.51 (1H, dd, J ) 7.3
and 14.3 Hz), 3.74 (1H, dd, J ) 3.7 and 11.6 Hz), 3.88 (1H,
dd, J ) 2.8 and 11.6 Hz), 4.28 (1H, ddd, J ) 2.8, 3.7, and 3.8
Hz), 4.34 (1H, ddd, J ) 6.1, 5.4, and 7.3 Hz), 5.73 (2H, br),
7.06-7.09 (2H, m), 7.11-7.14 (2H, m), 7.26-7.30 (1H, m), 7.44
and 8.45 (2H, each as s); FAB-MS m/z 588 (M+ + H). Anal.
Calcd for C28H45N5O3SSi2: C, 57.20; H, 7.72; N, 11.91. Found:
C, 57.39; H, 7.84; N, 11.81. Physical data of 17r: mp 195-
197 °C; UV (MeOH) λmax 260 nm (ꢀ 16400), λmin 237 nm (ꢀ
3′,5′-Bis-O-(ter t-bu tyld im eth ylsilyl)-2′-d eoxy-1′-C-p h en -
ylselen ou r id in e (13). This compound was obtained as a
mixture of two anomers (â/R ) 17/83) in 96% yield by using
15 equiv of PhSeH by the procedure described for the prepara-
tion of 6. HPLC (hexane/EtOAc ) 3/1) separation of this
mixture gave analytically pure 13â (tR 12.4 min, foam) and
13r (tR 10.8 min, solid). Physical data of 13â: UV (MeOH)
λmax 267 nm (ꢀ 10400), λmin 249 nm (ꢀ 7500); 1H NMR (CDCl3)
δ -0.01, 0.02, 0.09, and 0.11 (12H, each as s), 0.83 and 0.94
(18H, each as s), 2.89 (1H, dd, J ) 6.2 and 15.0 Hz), 2.94 (1H,
dd, J ) 3.2 and 15.0 Hz), 3.70 (1H, dd, J ) 3.6 and 11.2 Hz),
3.75 (1H, dd, J ) 3.2 and 11.2 Hz), 4.28-4.34 (2H, m), 5.15
1
6100); H NMR (CDCl3) δ -0.26, -0.11, 0.12, and 0.13 (12H,
each as s), 0.47 and 0.93 (18H, each as s), 2.65 (1H, dd, J )
5.5 and 14.0 Hz), 3.44 (1H, dd, J ) 6.6 and 10.9 Hz), 3.74 (1H,
dd, J ) 4.2 and 10.9 Hz), 3.75 (1H, dd, J ) 1.2 and 14.0 Hz),
4.19 (1H, ddd, J ) 1.3, 4.2, and 6.6 Hz), 4.40 (1H, ddd, J )
1.2, 1.3, and 5.5 Hz), 5.48 (2H, br), 7.16-7.19 (2H, m), 7.23-
6128 J . Org. Chem., Vol. 67, No. 17, 2002

1′-C-Phenylthio-2′-deoxynucleosides
7.26 (2H, m), 7.29-7.32 (1H, m), 7.60 and 8.44 (2H, each as
s); FAB-MS m/z 588 (M+ + H). Anal. Calcd for C28H45N5O3-
SSi2: C, 57.20; H, 7.72; N, 11.91. Found: C, 57.23; H, 7.78; N,
11.83.
H-2′) was obtained in 72% yield from 17 by the procedure
described for the preparation of 18, except that the reaction
was continued for 23 h after finishing addition of Bu3SnH.
HPLC (hexane/EtOAc ) 1/2) separation of this mixture gave
analytically pure 20â (tR 19.5 min, solid) and 20r (tR 22.8 min,
solid).
1′-C-Allyl-3′,5′-bis-O-(ter t-bu tyld im eth ylsilyl)-2′-d eoxy-
u r id in e (18â) a n d It’s r-An om er (18r). A mixture of 6 (100
mg, 0.18 mmol) and allyl(tributyl)tin (0.17 mL, 0.54 mmol) in
benzene (5 mL) was stirred at 80 °C under positive pressure
of dry Ar. To this was added a benzene (5 mL) solution of AIBN
(12 mg, 0.07 mmol) via a motor-driven syringe over 1 h. The
whole reaction mixture was heated with stirring for further 1
h. Evaporation of the solvent followed by column chromatog-
raphy (hexane/EtOAc ) 3/1) gave 18 (73.1 mg, 82%, â/R ) 68/
32, calculated by integrating H-5). Each anomer was isolated
by HPLC (hexane/EtOAc ) 5/1: 18â tR 41 min, foam; 18r tR
40 min, foam). Physical data of 18â: UV (MeOH) λmax 266 nm
Physical data of 20â: mp 155-158 °C; UV (MeOH) λmax 261
1
nm (ꢀ 13500), λmin 227 nm (ꢀ 1500); H NMR (CDCl3) δ 0.02,
0.03, and 0.05 (12H, each as s), 0.82 and 0.88 (18H, each as
s), 2.53 (1H, dd, J ) 5.5 and 13.6 Hz), 2.96-3.08 (3H, m), 3.69
(1H, dd, J ) 3.6 and 11.1 Hz), 3.76 (1H, dd, J ) 4.0 and 11.1
Hz), 4.06 (1H, ddd, J ) 3.6, 4.0, and 4.6 Hz), 4.35 (1H, ddd, J
) 4.6, 5.5, and 6.0 Hz), 4.85-4.98 (2H, m), 5.60-5.70 (1H, m),
5.96 (2H, br), 8.15 and 8.32 (2H, each as s); FAB-MS m/z 520
(M+ + H). Anal. Calcd for C25H45N5O3Si2: C, 57.76; H, 8.73;
N, 13.47. Found: C, 57.94; H, 9.02; N. 13.18. Physical data of
20r: mp 161-164 °C; UV (MeOH) λmax 261 nm (ꢀ 13600), λmin
1
(ꢀ 9400), λmin 232 nm (ꢀ 900); H NMR (CDCl3) δ 0.03, 0.04,
1
228 nm (ꢀ 1500); H NMR (CDCl3) δ -0.28, -0.11, and 0.10
0.07, and 0.08 (12H, each as s), 0.86 and 0.89 (18H, each as
s), 2.48 (1H, dd, J ) 3.9 and 14.3 Hz), 2.74 (1H, dd, J ) 6.3
and 14.3 Hz), 2.81 (1H, dd, J ) 6.0 and 14.2 Hz), 3.05 (1H,
dd, J ) 8.4 and 14.2 Hz), 3.62 (1H, dd, J ) 3.4 and 11.3 Hz),
3.69 (1H, dd, J ) 3.8 and 11.3 Hz), 4.08 (1H, ddd, J ) 3.4, 3.7,
and 3.8 Hz), 4.28 (1H, dd, J ) 3.7, 3.9, and 6.3 Hz), 5.04-5.10
(2H, m), 5.56 (1H, dd, J ) 1.5 and 8.4 Hz), 5.70-5.78 (1H, m),
7.88 (1H, d, J ) 8.4 Hz), 8.12 (1H, br); FAB-MS m/z 497 (M+
+ H), 535 (M+ + K). Anal. Calcd for C24H44N2O5Si2‚1/2H2O: C,
56.99; H, 8.77; N, 5.54. Found: C, 57.00; H, 8.87; N. 5.44.
Physical data of 18r: UV (MeOH) λmax 265 nm (ꢀ 10500), λmin
233 nm (ꢀ 2400); 1H NMR (CDCl3) δ -0.01 and 0.08 (12H, each
as s), 0.78 and 0.91 (18H, each as s), 2.25 (1H, dd, J ) 5.6 and
14.3 Hz), 2.63 (1H, dd, J ) 6.9 and 14.1 Hz), 2.94 (1H, dd, J
) 1.5 and 14.3 Hz), 3.05 (1H, dd, J ) 7.9 and 14.1 Hz), 3.59
(1H, dd, J ) 5.2 and 11.0 Hz), 3.70 (1H, dd, J ) 3.7 and 11.0
Hz), 3.99-4.02 (1H, m), 4.31 (1H, ddd, J ) 1.5, 1.8, and 5.6
Hz), 5.07-5.12 (2H, m), 5.62 (1H, dd, J ) 1.7 and 8.5 Hz),
5.67-5.75 (1H, m), 7.66 (1H, d, J ) 8.5 Hz), 8.14 (1H, br); FAB-
MS m/z 497 (M+ + H). Anal. Calcd for C24H44N2O5Si2: C, 58.02;
H, 8.93; N, 5.64. Found: C, 58.10; H, 9.14; N, 5.54.
(12H, each as s), 0.51 and 0.93 (18H, each as s), 2.37 (1H, dd,
J ) 5.8 and 14.0 Hz), 2.82 (1H, dd, J ) 7.2 and 14.0 Hz), 3.09
(1H, dd, J ) 7.2 and 14.0 Hz), 3.17 (1H, dd, J ) 0.8 and 14.0
Hz), 3.63 (1H, dd, J ) 5.6 and 11.0 Hz), 3.75 (1H, dd, J ) 3.6
and 11.0 Hz), 4.21 (1H, ddd, J ) 1.6, 3.6, and 5.6 Hz), 4.38
(1H, ddd, J ) 0.8, 1.6, and 5.8 Hz), 4.93-5.02 (2H, m), 5.49
(2H, br), 5.65-5.76 (1H, m), 8.03 and 8.33 (2H, each as s); FAB-
MS m/z 520 (M+ + H). Anal. Calcd for C25H45N5O3Si2: C, 57.76;
H, 8.73; N, 13.47. Found: C, 57.76; H, 8.94; N. 13.18.
3′,5′-Bis-O-(ter t-bu tyldim eth ylsilyl)-1′-C-(2-cyan o)eth yl-
2′-d eoxyu r id in e (21â) a n d It’s r-An om er (21r). A mixture
of 6 (100 mg, 0.18 mmol) and acrylonitrile (60 µL, 0.90 mmol)
in benzene (5 mL) was stirred at 80 °C under positive pressure
of dry Ar. To this was added a benzene (5 mL) solution of Bu3-
SnH (50 µL, 0.18 mmol) and AIBN (12 mg, 0.07 mmol) via a
motor-driven syringe over 1 h. The whole reaction mixture was
heated with stirring for further 1 h. Evaporation of the solvent
followed by column chromatography (hexane/EtOAc ) 3/1)
gave 21 (75.7 mg, 83%, â/R ) 74/26, calculated by integrating
H-5). HPLC (hexane/EtOAc ) 2/1) separation of this mixture
gave analytically pure 21â (tR 14.6 min, solid) and 21r (tR 16.8
min, solid). Physical data of 21â: mp 78-80 °C; UV (MeOH)
λmax 263 nm (ꢀ 11000), λmin 232 nm (ꢀ 3800); 1H NMR (CDCl3)
δ 0.02, 0.03, 0.08, and 0.09 (12H, each as s), 0.85 and 0.90
(18H, each as s), 2.33-2.39 (1H, m), 2.42-2.51 (2H, m), 2.57
(1H, dd, J ) 2.2 and 14.5 Hz), 2.65-2.71 (2H, m), 3.63 (1H,
dd, J ) 3.5 and 11.3 Hz), 3.68 (1H, dd, J ) 3.7 and 11.3 Hz),
4.19 (1H, ddd, J ) 3.5, 3.7, and 5.7 Hz), 4.31 (1H, ddd, J )
2.2, 2.5, and 5.7 Hz), 5.66 (1H, d, J ) 8.4 Hz), 7.90 (1H, d, J
) 8.4 Hz), 8.95 (1H, br); FAB-MS m/z 510 (M+ + H). Anal.
Calcd for C24H43N3O5Si2: C, 56.55; H, 8.50; N, 8.24. Found:
C, 56.73; H, 8.72; N. 8.24. Physical data of 21r: mp 186-188
°C; UV (MeOH) λmax 263 nm (ꢀ 10100), λmin 233 nm (ꢀ 3400);
1H NMR (CDCl3) δ -0.01 and 0.09 (12H, each as s), 0.78 and
0.91 (18H, each as s), 2.22-2.44 (4H, m), 2.82-2.87 (1H, m),
2.95 (1H, dd, J ) 1.3 and 14.3 Hz), 3.66 (1H, dd, J ) 4.5 and
11.2 Hz), 3.72 (1H, dd, J ) 3.1 and 11.2 Hz), 4.11 (1H, ddd, J
) 1.5, 3.1, and 4.5 Hz), 4.35 (1H, ddd, J ) 1.3, 1.4, and 1.5
Hz), 5.70 (1H, d, J ) 8.4 Hz), 7.64 (1H, d, J ) 8.4 Hz), 8.35
(1H, br); FAB-MS m/z 510 (M+ + H). Anal. Calcd for
1′-C-Allyl-3′,5′-b is-O-(ter t-b u t yld im et h ylsilyl)t h ym i-
d in e (19â) a n d It’s r-An om er (19r). A mixture of these two
anomers (19â/19r ) 68/32, calculated by integrating H-2′) was
obtained in 81% yield from 15 by the procedure described for
the preparation of 18, except that the reaction was continued
for 3 h after finishing addition of Bu3SnH. HPLC (hexane/
EtOAc ) 2/1) separation of this mixture gave analytically pure
19â (tR 9.4 min, foam) and 19r (tR 9.1 min, foam). Physical
data of 19â: UV (MeOH) λmax 270 nm (ꢀ 10200), λmin 238 nm
1
(ꢀ 2700); H NMR (CDCl3) δ 0.01, 0.03, 0.07, and 0.08 (12H,
each as s), 0.84 and 0.89 (18H, each as s), 1.89 (3H, d, J ) 1.2
Hz), 2.55 (1H, dd, J ) 2.8 and 15.0 Hz), 2.70 (1H, dd, J ) 6.0
and 15.0 Hz), 2.80 (1H, dd, J ) 6.3 and 15.0 Hz), 3.04 (1H,
dd, J ) 8.2 and 15.0 Hz), 3.61 (1H, dd, J ) 3.7 and 11.3 Hz),
3.65 (1H, dd, J ) 4.0 and 11.3 Hz), 4.11 (1H, ddd, J ) 3.4, 3.7,
and 4.0 Hz), 4.28 (1H, ddd, J ) 2.8, 3.4, and 6.0 Hz), 5.02-
5.08 (2H, m), 5.70-5.78 (1H, m), 7.65 (1H, q, J ) 1.2 Hz), 8.74
(1H, br); FAB-MS m/z 511 (M+ + H), 549 (M+ + K). Anal. Calcd
for C25H46N2O5Si2: C, 58.78; H, 9.08; N, 5.48. Found: C, 58.54;
H, 9.26; N. 5.35. Physical data of 19r: UV (MeOH) λmax 271
nm (ꢀ 10000), λmin 237 nm (ꢀ 2500); 1H NMR (CDCl3) δ -0.02,
-0.01, and 0.09 (12H, each as s), 0.76 and 0.92 (18H, each as
s), 1.90 (3H, d, J ) 1.2 Hz), 2.25 (1H, dd, J ) 5.9 and 14.3
Hz), 2.63 (1H, dd, J ) 6.9 and 14.0 Hz), 2.90 (1H, dd, J ) 2.0
and 14.3 Hz), 3.05 (1H, dd, J ) 7.7 and 14.0 Hz), 3.59 (1H,
dd, J ) 5.5 and 11.0 Hz), 3.70 (1H, dd, J ) 3.8 and 11.0 Hz),
4.01 (1H, ddd, J ) 1.9, 3.8, and 5.5 Hz), 4.28 (1H, ddd, J )
1.9, 2.0, and 5.9 Hz), 5.08-5.12 (2H, m), 5.66-5.75 (1H, m),
7.48 (1H, q, J ) 1.2 Hz), 7.93 (1H, br); FAB-MS m/z 549 (M+
+ K). Anal. Calcd for C25H46N2O5Si2: C, 58.78; H, 9.08; N, 5.48.
Found: C, 58.57; H, 9.23; N. 5.35.
C
24H43N3O5Si2: C, 56.55; H, 8.50; N, 8.24. Found: C, 56.82;
H, 8.75; N. 8.44.
3′,5′-Bis-O-(ter t-b u t yld im et h ylsilyl)-7-cya n o-5,6-d ih y-
d r o-6,1′-eth a n o-2′-d eoxyu r id in e (22). This compound (a
mixture of two diastereomers, ca. 1:0.4, stereochemistry not
known) was obtained in 41% yield as a powder by the
procedure described for the preparation of 21, except that Bu3-
SnH(1 equiv)/AIBN (0.4 equiv) was added dropwise over 4 h,
and that the reaction mixture was refluxed for 3 h after the
addition. FAB-MS m/z 510 (M+ + H). Anal. Calcd for
C
24H43N3O5Si2: C, 56.55; H, 8.50; N, 8.24. Found: C, 56.68;
H, 8.82; N. 8.31.
3′,5′-Bis-O-(ter t-bu tyld im eth ylsilyl)-1′-C-(2-ca r bom eth -
oxy)eth yl-2′-d eoxyu r id in e (23â) a n d It’s r-An om er (23r).
1′-C-Allyl-3′,5′-bis-O-(ter t-bu tyld im eth ylsilyl)-2′-d eoxy-
a d en osin e (20â) a n d It’s r-An om er (20r). A mixture of
these two anomers (20â/20r ) 71/29, calculated by integrating
J . Org. Chem, Vol. 67, No. 17, 2002 6129

Kumamoto et al.
A mixture of 6 (100 mg, 0.18 mmol), methyl acrylate (97 µL,
1.08 mmol), and Bu3SnH (50 µL, 0.18 mmol) in benzene (5 mL)
was stirred at 80 °C under positive pressure of dry Ar. To this
was added a benzene (5 mL) solution of AIBN (12 mg, 0.07
mmol) via a motor-driven syringe over 1 h. The whole reaction
mixture was heated with stirring for further 1 h. Evaporation
of the solvent followed by column chromatography (hexane/
EtOAc ) 3/1-1/1) gave 23 (70 mg, 72%, â/R ) 70/30, calculated
by integrating H-5). HPLC (hexane/EtOAc ) 2/1) separation
of this mixture gave analytically pure 23â (tR 26.4 min, solid)
and 23r (tR 30.0 min, solid). Physical data of 23â: mp 81-83
°C; UV (MeOH) λmax 264 nm (ꢀ 10300), λmin 232 nm (ꢀ 1400);
1H NMR (CDCl3) δ 0.02, 0.03, 0.06, and 0.08 (12H, each as s),
0.85 and 0.89 (18H, each as s), 2.23-2.30 (1H, m), 2.39-2.46
(2H, m), 2.52 (1H, dd, J ) 3.2 and 14.3 Hz), 2.66-2.72 (1H,
m), 2.71 (1H, dd, J ) 6.1 and 14.3 Hz), 3.61 (1H, dd, J ) 3.4
and 11.0 Hz), 3.63 (3H, s), 3.65 (1H, dd, J ) 3.8 and 11.0 Hz),
4.05 (1H, ddd, J ) 3.4, 3.5, and 3.8 Hz), 4.28 (1H, ddd, J )
3.2, 3.5, and 6.1 Hz), 5.60 (1H, dd, J ) 2.0 and 8.5 Hz), 7.89
(1H, d, J ) 8.5 Hz), 8.68 (1H, br); FAB-MS m/z 543 (M+ + H).
Anal. Calcd for C25H46N2O7Si2: C, 55.32; H, 8.54; N, 5.16.
Found: C, 55.43; H, 8.75; N. 5.14. Physical data of 23r: mp
133-136 °C; UV (MeOH) λmax 265 nm (ꢀ 10400), λmin 233 nm
1
(ꢀ 2500); H NMR (CDCl3) δ -0.01 and 0.08 (12H, each as s),
0.78 and 0.91 (18H, each as s), 2.15-2.29 (3H, m), 2.35-2.41
(1H, m), 2.75-2.81 (1H, m), 3.00 (1H, dd, J ) 1.6 and 14.5
Hz), 3.56 (1H, dd, J ) 5.3 and 11.0 Hz), 3.63 (3H, s), 3.68 (1H,
dd, J ) 3.5 and 11.0 Hz), 4.01 (1H, ddd, J ) 1.9, 3.5, and 5.3
Hz), 4.31 (1H, ddd, J ) 1.6, 1.9, and 5.5 Hz), 5.64 (1H, dd, J
) 2.5 and 8.4 Hz), 7.64 (1H, d, J ) 8.4 Hz), 7.98 (1H, br); FAB-
MS m/z 543 (M+ + H). Anal. Calcd for C25H46N2O7Si2: C, 55.32;
H, 8.54; N, 5.16. Found: C, 55.58; H, 8.70; N. 5.05.
J O0201934
6130 J . Org. Chem., Vol. 67, No. 17, 2002